Russia has one of the highest incidences of HIV among heroin addicted injection drug users (IDUs) in the world. Use of agonists for detoxification or maintenance is illegal, thus naltrexone is the only effective pharmacotherapy for preventing relapse and the associated HIV risk behaviors. Extended release (ER) naltrexone (Vivitrol(R)) has dramatically reduced heroin IDU and HIV risk in 12 and 24-week long trials in the U.S. and Russia. Our recent 24-week trial showed that an ER Naltrexone implant (Prodetoxone(R)) was superior to both placebo and oral naltrexone in preventing relapse, but that approximately half the patients who remained in treatment and did not relapse by the end of the 24-week treatment period, have relapsed and increased HIV risk behavior within months after ER Naltrexone treatment ended. The goal of this study is to answer the two critical questions on the most effective use of ER Naltrexone in the prevention of the spread of HIV: To what degree does extending the duration of treatment reduce relapse to drug use and HIV risk in heroin IDUs? This collaborative project between the University of Pennsylvania (UPENN) and the National Research Center on Addiction (NRCA) in Moscow, a PEPFAR site in the Russian Ministry of Health, is a prospective, randomized, placebo-controlled trial in which 130 HIV-negative, detoxified, consenting heroin IDUs who shared drug injection equipment within the last year, will be randomized to a 48-week course of injectable ER Naltrexone (Vivitrol) or 24 weeks of Vivitrol followed by additional 24 weeks of placebo Vivitrol. Both cohorts will have bi-weekly counseling for 48 weeks and follow-up assessments at weeks 60 and 72. Primary outcomes are the proportion of patients who relapsed during the week 48 to 72 follow-up period and reduction in HIV injecting risk behaviors. Secondary outcomes are 1) opioid positive urine drug screens~ 2) HIV sex risk behaviors~ 3) Time to relapse~ 4) Proportion of appointments kept~ 5) Psychiatric symptoms~ 6) Opioid craving~ 7) Self-reported drug use~ 8) Money spent for drugs~ 9) Employment~ 10) Arrests~ 11) Overall adjustment~ 12) Adverse events. Hypotheses: 1) Patients randomized to the 48-week Vivitrol condition will have significantly better outcomes on the primary and secondary outcomes than those in the 24-week Vivitrol plus 24-week placebo condition~ 2) Five or more secondary outcomes will favor the 48-week condition~ and none will favor the 24-week condition. PUBLIC HEALTH RELEVANCE: This prospective, placebo-controlled, randomized trial is collaboration between the University of Pennsylvania and the National Center for Addictions Research (NRCA) in Moscow, Russia. It will compare a 24-week course of injectable extended release (ER) naltrexone (Vivitrol) plus a 24-week course of Vivitrol placebo, with a 48-week course of Vivitrol, in opioid dependent patients seeking treatment at the NRCA, who have shared drug injection equipment in the past year. The project aims to determine whether a longer course of Vivitrol results in less relapse to drug use and HIV drug risk behaviors that the shorter course.